High αv integrin level of cancer cells is associated with development of brain metastasis in athymic rats

Yingjen Jeffrey Wu, Michael A. Pagel, Leslie Muldoon, Rongwei (Rochelle) Fu, Edward Neuwelt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background/Aim: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion: αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.

Original languageEnglish (US)
Pages (from-to)4029-4040
Number of pages12
JournalAnticancer Research
Volume37
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Nude Rats
Integrins
Neoplasm Metastasis
Brain
Neoplasms
Cell Movement
Cell Adhesion
Cell Migration Assays
Skin Neoplasms
Lung Neoplasms
Proteins
Animal Models

Keywords

  • Brain metastasis
  • Breast cancer
  • Integrin
  • Intetumumab
  • Lung cancer
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

High αv integrin level of cancer cells is associated with development of brain metastasis in athymic rats. / Wu, Yingjen Jeffrey; Pagel, Michael A.; Muldoon, Leslie; Fu, Rongwei (Rochelle); Neuwelt, Edward.

In: Anticancer Research, Vol. 37, No. 8, 01.08.2017, p. 4029-4040.

Research output: Contribution to journalArticle

@article{fc115af5e74b451f8e89d19cbb6a5e9d,
title = "High αv integrin level of cancer cells is associated with development of brain metastasis in athymic rats",
abstract = "Background/Aim: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion: αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.",
keywords = "Brain metastasis, Breast cancer, Integrin, Intetumumab, Lung cancer, Melanoma",
author = "Wu, {Yingjen Jeffrey} and Pagel, {Michael A.} and Leslie Muldoon and Fu, {Rongwei (Rochelle)} and Edward Neuwelt",
year = "2017",
month = "8",
day = "1",
doi = "10.21873/anticanres.11788",
language = "English (US)",
volume = "37",
pages = "4029--4040",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "8",

}

TY - JOUR

T1 - High αv integrin level of cancer cells is associated with development of brain metastasis in athymic rats

AU - Wu, Yingjen Jeffrey

AU - Pagel, Michael A.

AU - Muldoon, Leslie

AU - Fu, Rongwei (Rochelle)

AU - Neuwelt, Edward

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background/Aim: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion: αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.

AB - Background/Aim: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion: αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.

KW - Brain metastasis

KW - Breast cancer

KW - Integrin

KW - Intetumumab

KW - Lung cancer

KW - Melanoma

UR - http://www.scopus.com/inward/record.url?scp=85026235904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026235904&partnerID=8YFLogxK

U2 - 10.21873/anticanres.11788

DO - 10.21873/anticanres.11788

M3 - Article

VL - 37

SP - 4029

EP - 4040

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 8

ER -